Association of neutrophil-to-lymphocyte ratio, radiotherapy fractionation/technique, and risk of development of distant metastasis among patients with locally advanced rectal cancer

Gowoon Yang, Jee Suk Chang, Jeong Eun Choi, Eun Sil Baek, Seung-Seob Kim, Hwa Kyung Byun, Yeona Cho, Woong Sub Koom, Seung Yoon Yang, Byung Soh Min, Sang Joon Shin, Gowoon Yang, Jee Suk Chang, Jeong Eun Choi, Eun Sil Baek, Seung-Seob Kim, Hwa Kyung Byun, Yeona Cho, Woong Sub Koom, Seung Yoon Yang, Byung Soh Min, Sang Joon Shin

Abstract

Background: We investigated the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) in patients with locally advanced rectal cancer (LARC) and whether modifiable factors in radiotherapy (RT) influenced the NLR.

Methods: Data of 1386 patients who were treated with neoadjuvant RT and concurrent or sequential chemotherapy for LARC between 2006 and 2019 were evaluated. Most patients (97.8%) were treated with long-course RT (LCRT; 50-50.4 Gy in 25-28 fractions) using three-dimensional conformal radiotherapy (3D-CRT) (n = 851) or helical tomotherapy (n = 504), and 30 patients underwent short-course RT (SCRT; 25 Gy in 5 fractions, followed by XELOX administration for 6 weeks). Absolute neutrophil and lymphocyte counts were obtained at initial diagnosis, before and during the preoperative RT course, and after preoperative concurrent chemoradiotherapy. The primary endpoint was distant metastasis-free survival (DMFS).

Results: The median follow-up time was 61.3 (4.1-173.7) months; the 5-year DMFS was 80.1% and was significantly associated with the NLR after RT but not before. A post-RT NLR ≥ 4 independently correlated with worse DMFS (hazard ratio, 1.42; 95% confidence interval, 1.12-1.80), along with higher ypT and ypN stages. Post-RT NLR (≥ 4) more frequently increased following LCRT (vs. SCRT, odds ratio [OR] 2.77, p = 0.012) or helical tomotherapy (vs. 3D-CRT, OR 1.29, p < 0.001).

Conclusions: Increased NLR after neoadjuvant RT is associated with increased distant metastasis risk and poor survival outcome in patients with LARC. Moreover, high NLR following RT is directly related to RT fractionation, delivery modality, and tumor characteristics. These results are hypothesis-generating only, and confirmatory studies are required.

Keywords: Distant metastasis-free survival; Lymphocyte; Neutrophil; Poor outcome; Rectal neoplasm.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
a OS in patients with low-post RT NLR versus high post-RT NLR. Cox-adjusted survival curve demonstrating overall survival in patients with low post-radiotherapy (RT) neutrophil-to-lymphocyte ratio (NLR) vs. high post-RT NLR using Cox proportional hazard models (adjusted for age, sex, clinical T stage, clinical N stage, RT modality, ypT, ypN, adjuvant chemotherapy, RT fractionation). b DMFS in patients with low-post RT NLR versus high post-RT NLR. Cox-adjusted survival curve demonstrating distant metastasis-free survival in patients with low post-RT neutrophil-to-lymphocyte ratio (NLR) vs. high post-RT NLR using Cox proportional hazard models (adjusted for age, sex, clinical T stage, clinical N stage, RT modality, ypT, ypN, adjuvant chemotherapy, RT fractionation)
Fig. 2
Fig. 2
a Chi-square test for post-RT NLR and pCR rate. Association between post-radiotherapy (RT) neutrophil-to-lymphocyte ratio (NLR) and the pathologic complete response rate per the chi-square test. b Chi-square test for post-RT NLR and NAR. Association between post-RT neutrophil-to-lymphocyte ratio (NLR) and the neoadjuvant rectal score per the chi-square test
Fig. 3
Fig. 3
LRFS in patients with low post-RT NLR versus high post-RT NLR. Kaplan–Meier estimates of local recurrence-free survival in patients with low post-radiotherapy (RT) neutrophil-to-lymphocyte ratio (NLR) vs. high post-RT NLR

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Source: PubMed

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